Losartan to Reverse Sickle Nephropathy

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Children's Hospital Medical Center, Cincinnati
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT01479439
First received: November 16, 2011
Last updated: April 8, 2014
Last verified: April 2014

November 16, 2011
April 8, 2014
February 2012
December 2014   (final data collection date for primary outcome measure)
Changes from baseline albuminuria [ Time Frame: Assessed at weeks 2, 4, 8, 12, and 26. ] [ Designated as safety issue: No ]
A ≥25% reduction in urine albumin from baseline in ≥ 30% of the subjects in the MiA group.
Same as current
Complete list of historical versions of study NCT01479439 on ClinicalTrials.gov Archive Site
  • Change from baseline in urine osmolality [ Time Frame: Assessed at weeks 12 and 26. ] [ Designated as safety issue: No ]
    A significant improvement in UOsm in the NoA group.
  • No changes in category of albuminuria (NoA, MiA or MaA) [ Time Frame: Assessed at weeks 2, 4, 8, 12, and 26 ] [ Designated as safety issue: No ]
    It is likely that the intervention may halt the progression of NoA to MiA or MiA to MaA, and albuminuria would have worsened if there was no intervention. Therefore, the hypothesis is that there will be no change in the category of albuminuria.
  • Identification of novel biomarkers [ Time Frame: Assessed at baseline and weeks 4, 12, and 26 ] [ Designated as safety issue: No ]
    A significant association of KIM-1 and NAG biomarkers with renal function (albuminuria and UCD).
  • Serum Cystatin C [ Time Frame: Assessed at screening, baseline and weeks and weeks 2, 4, 8, 12, and 26 ] [ Designated as safety issue: No ]
    A significant association of creatinine clearance with cystatin C estimated GFR
Same as current
Not Provided
Not Provided
 
Losartan to Reverse Sickle Nephropathy
A Phase II Trial of Losartan to Reverse Sickle Nephropathy

Sickle cell disease causes kidney damage with increasing age, leading to chronic kidney disease and renal failure in nearly one third of patients with sickle cell disease. Currently, there is no treatment for sickle cell related kidney disease. The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.

Not Provided
Interventional
Phase 2
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Nephropathy
  • Sickle Cell Anemia
Drug: Losartan
Form: suspension, tablet. Dosage & frequency: age 6-16 = 0.7mg/kg once daily; age >16 = 50mg once daily. Duration: 6 months
Experimental: Sickle cell disease
The purpose of this research study is to see if losartan can help reduce or reverse damage done to the kidneys of children and adults with Sickle Cell Anemia (SCA) and Sickle Beta-zero (HbSβ0) Thalassemia.
Intervention: Drug: Losartan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
54
July 2015
December 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Age ≥6 years of age; for no albuminuria (NoA) group age is ≥ 6 years and <21 years of age
  2. Diagnosis of hemoglobin SS disease or Sβ0 thalassemia by hemoglobin electrophoresis and/or β-globin gene mapping.
  3. Urine osmolality <700 mOsm on first morning urine
  4. Written informed consent (and assent, where applicable)
  5. Documented urine albumin levels showing either

    • NoA:,.UAlb <30mg/g creatinine on a first morning urine
    • MiA: UAlb 30-300 mg/g creatinine on a first morning urine or
    • MaA: UAlb >300 mg/g creatinine on a first morning urine sample
  6. A documented negative serum pregnancy test for females with child bearing potential or greater than 10 years of age within (prior to) 7 days of starting the study medication.
  7. Subjects with child-bearing potential must be willing to use a medically accepted form of contraception throughout the study.
  8. Patients on hydroxyurea who are on a stable (not changing) dose of HU for three months prior to study entry.

Exclusion Criteria:

  1. Patients with Hb SC, SD, Sβ+thal, SE and other sickle hemoglobinopathies, and sickle trait (AS).
  2. Pregnant or lactating females, or females of child-bearing potential that are unable to use a medically accepted form of contraception throughout the study.
  3. Urine creatinine clearance (Clcr) <60 mL/minute/1.73 m2
  4. Gross (not microscopic) hematuria. If hematuria has resolved for 2 weeks or more, patients will be eligible.
  5. Hyperkalemia (K≥5.5) at baseline despite a low potassium diet
  6. Concurrent condition that predisposes to nephropathy, such as lupus, diabetes, and hypertension, not controlled with medications..
  7. On a renin-angiotensin pathway inhibitor (e.g., captopril, lisinopril, Losartan, valsartan, etc) for the last two weeks prior to enrollment.
  8. Hypersensitivity to Angiotensin II receptor blockers such as losartan, valsartan, telmisartan.
  9. Patients on red cell apheresis or ongoing aggressive chronic transfusions (one or more a month with a goal of HbS < 30%). Patients receiving a simple transfusion for symptoms during acute event will be eligible, but if they receive a partial or full exchange transfusion during an acute event, then they will only be eligible after 90 days.
  10. Hepatic dysfunction defined as ALT or direct bilirubin > 3X upper limit of normal (ULN).
  11. Chronic therapy with NSAIDS or Cox2 inhibitors
  12. On another interventional trial. May be eligible two weeks after completion of another interventional study.
  13. Any condition that interferes with the ability of the patient to understand or comply with the treatment plan and follow up.
  14. A serious mental or physical illness or a major disease (cardiac, renal, hepatic, neurological, endocrine, metabolic, pulmonary function or psychiatric), which in the opinion of the investigator would compromise participation in the study.
  15. Unable to take oral medications.
  16. HIV confirmed positive.
  17. Chronic therapy with steroids. May be eligible after three weeks of completing steroid therapy.
  18. Patients on lithium will be excluded
Both
6 Years and older
No
Contact: Tamara Nordheim, RN 513-636-7374 tamara.nordheim@cchmc.org
United States
 
NCT01479439
2010-3070
Yes
Children's Hospital Medical Center, Cincinnati
Children's Hospital Medical Center, Cincinnati
Not Provided
Principal Investigator: Punam Malik, M.D. Children's Hospital Medical Center, Cincinnati
Children's Hospital Medical Center, Cincinnati
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP